Increased inflammatory markers correlate with liver damage and predict severe COVID-19: a systematic review and meta-analysis

This study aimed to determine whether patients with elevated CRP, TNFα, and IL-6 levels may be at increased risk for severe infection and liver damage of COVID-19. Background: The COVID-19 outbreak is a serious health problem to human beings. The evidence suggests that inflammatory markers related to liver damage increase in severe forms of COVID-19 compared to mild cases. Methods: The electronic databases ISI Web of Science, EMBASE, and Cochrane Library were comprehensively searched for articles published up to May, 2020. Data from each identified study was combined using the random effects model to estimate standardized mean difference (SMD) and 95% confidence intervals (95% CIs). Sensitivity and publication bias were also calculated. Results: Totally, 23 studies were included in this meta-analysis comprising 4313 patients with COVID-19. The random effects results demonstrated that patients with severe COVID-19 had significantly higher levels of CRP [SMD = 3.26 mg/L; (95% CI 2.5, 3.9); p<0.05; I2 = 98.02%; PHeterogeneity = 0.00], TNFα [SMD = 1.78 ng/mL; (95% CI 0.39, 3.1); p=0.012; I2 = 98.2%; PHeterogeneity = 0.00], and IL-6 [ SMD = 3.67 ng/mL; (95% CI 2.4, 4.8); p<0.05; I2 = 97.8%; PHeterogeneity = 0.00] compared with those with the mild form of the disease. Significant heterogeneity was present. No significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Conclusion: The data suggests that enhanced inflammation may be associated with COVID-19-related liver damage, possibly involving inflammatory marker-related mechanisms.